The Castilian Spanish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Castilian Spanish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability and construct validity (convergent and discriminant validity). A total of 526 JIA patients (8.6% systemic, 49.4% oligoarticular, 18.2% RF negative polyarthritis, 23.8% other categories) and 78 healthy children, were enrolled in six centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Castilian Spanish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practise and clinical research.

Outpatients with acute osteoarticular infections had favourable outcomes when they received just oral antibiotics without intravenous antibiotics.

AIM: The traditional approach for acute paediatric osteoarticular infections (OAI) has comprised initial intravenous antibiotics followed by prompt oral antibiotics. We assessed how providing just oral antibiotics compared to the traditional two-step approach. METHODS: This prospective study was performed at the Hospital La Paz, Madrid, Spain, from September 2015 to September 2016. We compared 25 outpatients, with good general health and a mean age of 25 months who received just oral antibiotics, with 228 hospitalised children of a similar age who received intravenous and oral antibiotics from other hospitals in the Spanish Network of Osteoarticular Infections. RESULTS: The groups were comparable in terms of age, sex, fever, erythrocyte sedimentation rate value, C-reactive protein and diagnosis. The oral group comprised 15 with osteomyelitis, seven with septic arthritis, two with osteoarthritis and one with spondylodiscitis. This group had a lower percentage of Staphylococcus aureus (8% vs 26%, p = 0.06) and higher proportion of Kingella kingae (24% vs 9%, p = 0.017) than the intravenous group. There were complications (24%) and follow-up sequelae (6%) in the intravenous group, but none in the oral group. CONCLUSION: Outpatients with OAI who were in good general health had favourable outcomes when they received oral antibiotics without intravenous antibiotics.

Corrigendum: Minimally invasive management of pediatric osteoarticular infections.

[This corrects the article DOI: 10.3389/fped.2022.1017035.].

Severe Thrombocytopenia as the Main Manifestation of Childhood-Onset Systemic Lupus Erythematosus.

Thrombocytopenia is a common hematologic abnormality of childhood-onset systemic lupus erythematosus (cSLE). Although in most cases thrombocytopenia is mild, severe thrombocytopenia with bleeding complications might occur, and is further correlated with disease activity and a worse prognosis. We report two female patients with severe thrombocytopenia as the initial manifestation of cSLE, which were successfully treated by intensive immunosuppression including several high-dose methylprednisolone pulses and IV cyclophosphamide. Both patients were initially diagnosed with idiopathic thrombopenic purpura (ITP) refractory to conventional treatment and complicated with haemorrhagic manifestations. For this matter, patients with ITP should be assessed for the presence of ANA, anti-dsDNA antibodies, and complement levels, since they are at high risk to develop cSLE.

Clinical course and seroprevalence of COVID-19 in children with rheumatic diseases-cross-sectional study from a reference centre in Spain.

SARS-CoV-2 infections in children are frequently asymptomatic or mild and can go unnoticed. This study aimed to describe the seroprevalence and clinical course of SARS-CoV-2 in a cohort of children with rheumatic diseases in a real-life setting and assess possible risk factors. A cross-sectional study was performed in a paediatric rheumatology unit (September 2020 to February 2021). At inclusion, a specific questionnaire was completed and SARS-CoV-2 serology was performed. Demographics, treatment and disease activity of patients with and without laboratory-confirmed SARS-CoV-2 infection were compared. A total of 105 children were included. SARS-CoV-2 infection was demonstrated in 27 patients (25.7%). The mean age was 11.8 years, and most patients were females (72.4%). The most frequent underlying condition was juvenile idiopathic arthritis (70.3%; 19/27). Patients received immunosuppressive treatment in 78% of cases (21/27). Overall, 44.4% (12/27) of infected patients were asymptomatic. A total of 66.7% (18/27) of patients did not require medical assistance. Three patients required hospital admission because of COVID-19. Children with confirmed SARS-CoV-2 infection were less frequently in remission (52% vs 72%; p 0.014). Moderate disease activity and treatment with oral corticosteroids were associated with higher risk for SARS-CoV-2 (OR 5.05; CI 95%: 1.56-16.3 and OR 4.2; CI 95%: 1.26-13.9, respectively). In a cohort of Spanish paediatric patients with rheumatic diseases, clinical course of COVID-19 was mild, with more than one third of asymptomatic cases. Higher disease activity and oral corticosteroids appear to be risk factors for SARS-CoV-2 infection. Key Points • We aimed to investigate the seroprevalence of SARS-CoV-2 infection in a cohort of Spanish paediatric patients with RD, testing both symptomatic and asymptomatic patients. We also compared treatment and disease activity of patients with and without laboratory-confirmed SARS-CoV-2 infection. • In our cohort of 105 paediatric patients with rheumatic diseases, the clinical course of COVID-19 was mild and 44% of cases were asymptomatic. Three cases required hospital admission with no complications. Seroprevalence was 20%. • No association was found between disease activity or treatment with corticosteroids and symptomatic or asymptomatic infection. Higher disease activity and treatment with oral corticosteroids appeared to be risk factors for laboratory-confirmed SARS-CoV-2 infection.

Are infections in children with juvenile idiopathic arthritis more frequent than in healthy children? A prospective multicenter observational study.

Background: Children with juvenile idiopathic arthritis (JIA) might be at a higher risk of infection. Our objectives are to describe and compare infection rates in patients with JIA vs. healthy patients. Methods: A prospective, multicenter observational study was performed in Spain from January 2017 to June 2019. Patients with JIA from 7 participating hospitals and children without JIA (siblings of patients with JIA, and non-JIA children from primary health centers) were followed up with quarterly questionnaires to record infection episodes. Tuberculosis, herpes zoster, and infections requiring hospital admission were considered severe infections. Rates of infection (episodes/patient/year) were compared using a generalized estimating equations model. Results: A total of 371 children (181 with and 190 without JIA) were included. The median age was 8.8 years (IQR 5.5-11.3); 75% of the patients with JIA received immunosuppressive treatment (24% methotrexate, 22% biologic, 26% both). A total of 667 infections were recorded; 15 (2.2%) were considered severe. The infection rate was 1.31 (95%CI 1.1-1.5) in JIA and 1.12 (95%CI 0.9-1.3) in non-JIA participants (p = 0.19). Age <4 years increased the infection rate by 2.5 times (2.72 vs. 1.12, p < 0.001) in both groups. The most frequent infection sites were upper respiratory (62.6% vs. 74.5%) and gastrointestinal (18.8% vs. 11.4%). There were no differences in severe infections (2.5% vs. 2%, p = 0.65) between the groups. In children with JIA, younger age and higher disease activity (JADAS71) were associated with a higher infection rate. Conclusion: We found no differences in the infection rate or infection severity between patients with and without JIA. Most infections were mild. An age younger than 4 years increased the infection risk in both groups. Higher disease activity was associated with a higher infection rate.

Biological therapy in refractory chronic nonbacterial osteomyelitis: A case series of 19 patients.

INTRODUCTION: Chronic non-bacterial osteomyelitis (CNO) represents an autoinflammatory bone disorder. Currently there are no standardized diagnostic or treatment guidelines. The objective of the study is to describe our experience with biological therapy in children with the disease. METHODS: Retrospective chart review of patients with CNO treated with biological therapy followed at two tertiary hospitals from January 2007 to April 2020. Biologicals were started in most patients due to persistent disease activity after receiving standard therapy with at least 2 drugs (NSAIDs and corticosteroids and/or pamidronate). RESULTS: Twenty-five patients were diagnosed with CNO. Out of those, 19 patients (15 females) failed conventional therapy. The mean age at diagnosis was 8.8±2.9 years and the mean diagnostic delay was 6.9±8.3 months. All patients presented with bone pain and 6/19 also had fever. The most frequently affected bones were femur (9 patients), followed by clavicle, tibia and vertebrae (6, 6 and 5 patients respectively). Nine children had skin lesions. C-reactive protein was elevated in 13/19 patients (mean 20.2mg/L±11.7) and ESR in 16/19 (mean 48mm/h±29). All patients received nonsteroidal anti-inflammatory drugs, 15/19 pamidronate, 10/19 corticosteroids and 19 anti-TNF-therapy. At the last follow-up visit, 10/19 patients were still on biological therapy (8 adalimumab, 2 infliximab) and 18 out of 19 remained asymptomatic. In regards to adverse effects, one patient receiving infliximab developed S. aureus osteomyelitis and another cutaneous leishmaniosis. CONCLUSIONS: This research emphasizes that anti-TNF-therapy represents an effective and safe alternative for patients with CNO refractory to conventional treatments.

Colchicine treatment in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome: A multicenter study in Spain.

OBJECTIVE: To evaluate the efficacy of colchicine therapy in pediatric patients with PFAPA syndrome who present with an incomplete response to the standard treatment or with frequent episodes (an interval of less than 14 days between two disease flares). METHODS: A multicenter cohort study of children diagnosed with PFAPA syndrome and treated with colchicine was performed in three separate hospitals located in Spain. The patients clinical and laboratory data were reviewed by accessing their medical records. Response to colchicine was evaluated after 12 months of treatment for frequency, duration, and intensity of PFAPA episodes. RESULTS: A total of 13 children were included in our study, 43% of whom were boys. Median age of the colchicine therapy initiation was 6 years (interquartile range (IQR)=3-9.5). Following a 12-month period of colchicine therapy (median dosage of 0.02 mg/kg/day; IQR=0.02-0.03), a significant decrease in the median number of flares (median 8; IQR=7-14 vs 3; IQR=2-4; p=0.005) and the duration of disease episodes (median 4 days; IQR=3.25-5.125 vs 1 day; IQR=1-2; p=0.003) was observed. Furthermore, the highest degree of fever during disease flares was reduced from median 40ºC (IQR=39.5-40) to 38.5ºC (IQR=37.7-38.9) (p=0.002). CONCLUSION: Colchicine therapy decreased the frequency and intensity of PFAPA. The use of colchicine could be an effective treatment in pediatric patients with PFAPA syndrome who present with frequent or severe relapses.

Fatal outcome of anti-MDA5 juvenile dermatomyositis in a paediatric COVID-19 patient: a case report.

Anti-melanoma differentiation-associated gene 5 juvenile dermatomyositis (anti-MDA5 JDM) is associated with high risk of developing rapidly progressive interstitial lung disease (RP-ILD). Here we report an 11-year-old girl with anti-MDA5 JDM and RP-ILD which led to a fatal outcome, further aggravated by SARS-CoV-2 infection. She was referred to our hospital after being diagnosed with anti-MDA5 JDM and respiratory failure due to RP-ILD. On admission, fibrobronchoscopy with bronchoalveolar lavage (BAL) revealed Pneumocystis jirovecii infection so treatment with intravenous trimethoprim-sulfamethoxazole was initiated. Due to RP-ILD worsening, immunosuppressive therapy was intensified using methylprednisolone pulses, cyclophosphamide, tofacitinib and intravenous immunoglobulin without response. She developed severe hypoxemic respiratory failure, pneumomediastinum and pneumothorax, further complicated with severe RP-ILD and cervical subcutaneous emphysema. Three real-time RT-PCR for SARS-CoV-2 were made with a negative result. In addition, she was complicated with a secondary hemophagocytic lymphohistiocytosis and a fourth real-time PCR for SARS-CoV-2 performed in BAS sample was positive. Despite aggressive treatment of RP-ILD due to anti-MDA5 JDM, there was no improvement of respiratory failure in the following days and patient developed refractory septic shock and died. Anti-MDA5 JDM patients with RP-ILD have a poor prognosis with a high mortality rate. For this reason, intensive immunosuppressive therapy is essential including the use of promising drugs such as tofacitinib. COVID-19 in children with underlying health conditions like anti-MDA5 JDM may still be at risk for disease and severe complications.

Sacroilitis in Preschool Children: A Case Series and Review of the Literature.

Pyogenic sacroilitis is an infrequent osteoarticular infection, and its diagnosis is a challenge in young children. A series of 20 cases is described. The median age was 15 months, 75% of them being under 2 years old. Fourteen (70%) reported fever. Refusal to sit was the main reason for consultation. Final diagnosis was confirmed by bone scintigraphy. All patients achieved a complete resolution without sequelae.

Biallelic loss-of-function LACC1/FAMIN Mutations Presenting as Rheumatoid Factor-Negative Polyarticular Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease with both autoimmune and autoinflammatory components. Recently, familial cases of systemic-onset JIA have been attributed to mutations in LACC1/FAMIN. We describe three affected siblings from a Moroccan consanguineous family with an early-onset chronic, symmetric and erosive arthritis previously diagnosed as rheumatoid factor (RF)-negative polyarticular JIA. Autozygosity mapping identified four homozygous regions shared by all patients, located in chromosomes 3, 6 (n:2) and 13, containing over 330 genes. Subsequent whole exome sequencing identified two potential candidate variants within these regions (in FARS2 and LACC1/FAMIN). Genotyping of a cohort of healthy Moroccan individuals (n: 352) and bioinformatics analyses finally supported the frameshift c.128_129delGT mutation in the LACC1/FAMIN gene, leading to a truncated protein (p.Cys43Tyrfs*6), as the most probable causative gene defect. Additional targeted sequencing studies performed in patients with systemic-onset JIA (n:23) and RF-negative polyarticular JIA (n: 44) revealed no pathogenic LACC1/FAMIN mutations. Our findings support the homozygous genotype in the LACC1/FAMIN gene as the defect underlying the family here described with a recessively inherited severe inflammatory joint disease. Our evidences provide further support to the involvement of LACC1/FAMIN deficiency in different types of JIA in addition to the initially described systemic-onset JIA.

Epidemiology and Management of Acute, Uncomplicated Septic Arthritis and Osteomyelitis: Spanish Multicenter Study.

BACKGROUND: Acute osteoarticular infection (OAI) is a potentially severe disease. The aim of this study was to evaluate the etiology, clinical characteristics and therapeutic approach of OAI in children in Spain. METHODS: Medical records from children <14 years with OAI from 25 hospitals between 2008 and 2012 were reviewed. Confirmed osteomyelitis (OM) and septic arthritis (SA) required a positive bacterial isolate; otherwise, they were considered probable. Probable SA with <40,000 cells/mm in joint fluid was not included. RESULTS: A total of 641 children were evaluated. Two hundred and ninety-nine cases (46%) were OM, 232 (36%) SA, 77 (12%) osteoarthritis and 33 (5%) spondylodiscitis. Children with OM were older (63 vs. 43 months for SA; P < 0.001). Magnetic resonance imaging and bone scintigraphy had the highest yield for OM diagnosis (94%). Arthrocentesis was performed in 96% of SA. A microorganism was isolated in 246 patients (38%: 33% OM vs. 55% SA; P < 0.001): Staphylococcus aureus was the most common (63%), followed by Kingella kingae (15%) and Streptococcus pyogenes (9%). Ninety-five percent of children initially received IV antibiotics, mostly cefotaxime + cloxacillin (60%) or cloxacillin (40%). Total treatment duration was 38 (±31) days for OM and 28 (±16) days for SA (P < 0.0001). Twenty percent of children with OM (46% because of complications) and 53% with SA (95% initial arthrotomy) underwent surgery. Patients with SA were compared according to initial arthrotomy (n = 123) versus arthrocentesis (n = 109), and no clinical differences were observed, except for higher rate of hip SA in the former (50% vs. 9%; P < 0.001). Children with arthrocentesis had less sequelae [6.6% vs. 1%; P = 0.03, odds ratio = 0.58 (95% confidence interval: 0.45-0.76)], but not in the multivariate analysis. CONCLUSIONS: This is the largest pediatric cohort of OAI in Spain. S. aureus was the most common isolate, although K. kingae was recovered in a high proportion of cases. Conservative management was applied in half of the patients. There was a low rate of sequelae, even with nonsurgical approaches.